H.  Grimes

H. Leighton Grimes

Professor, Department of Pediatrics, UC College of Medicine
Director, Cancer Pathology Program of the Division of Experimental Hematology and the Division of Pathology, Co-Leader Program in Hematologic Malignancies, Cincinnati Children's Hospital

Childrens Hospital Bldg R

S5.224

COM Pediatrics Immunobiology - 0054

Cincinnati Children's Hospital
Division of Immunobiology

Professional Summary

I have a broad background in hematopoiesis, molecular biology, and molecular oncology including mouse modeling of hematopoiesis, myelopoiesis, marrow failure syndromes and leukemia. I received a PhD in Molecular Pathology and Immunology studying gene regulation with Maureen Goodenow (then at University of Florida), then joined Philip Tsichlis (then at Fox Chase Cancer Center) at the time the lab was cloning novel genes activated by Moloney murine leukemia virus insertion mutagenesis (e.g. Akt, Tpl2). I participated in the identification of the Growth factor independent-1 (Gfi1) transcription factor, its DNA binding specificity, named the “SNAG” transcription repressor domain, and genetically linked this domain to Gfi1-directed biology.  My laboratory continues to focus on transcriptional integration of normal and malignant hematopoiesis.  With Marshall Horwitz (U. Wash) we identified humans with mutations in GFI1, who display severe congenital neutropenia (SCN) and non-immune chronic idiopathic neutropenia of adults (NI-CINA). 

Research and Practice Interests

Recently, I collaborated with Jose Cancelas (CCHMC) and Carolyn Lutzko (CCHMC) to generate iPSC from SCN patients, and to clearly demonstrate the role of mutant-neutrophil elastase in the pathogenesis of SCN.  We are currently focused upon dissecting the transcriptional and epigenetic programming engendered by both normal and SCN-mutant Gfi1. To this end we have generated deep single cell RNA Seq (scRNA Seq) data sets from bone marrow stem/progenitor cells, and have collaborated with Nathan Salomonis (CCHMC) to develop Iterative Clustering and Guide Gene Selection (ICGS), a novel bioinformatics tool for unsupervised scRNA Seq analysis. ICGS is capable of identifying key genes within the data sets, elaborating clusters correlated to these genes, and then ordering cells.  In Nature, we (Grimes, Salomonis and Harinder Singh) recently completed a study dissecting homeostatic myeloid development to resolve deep molecular insight into the process of differentiation.  In Cancer Discovery, we recently demonstrated a rapid, fully penetrant model of cytogenetically normal AML, and performed scRNA Seq and ICGS to dissect AML clonality.  By mapping the AML data onto the normal hematopoietic scRNA Seq data we were able to rapidly identify the clonal AML population and uncover leukemia-stem-cell transcriptional programming. Thus, the ICGS algorithm and our deep scRNA Seq data sets facilitate deep mechanistic insight into biological questions.

Publications

Peer Reviewed Publications

Velu, Chinavenmeni S; Chaubey, Aditya; Phelan, James D; Horman, Shane R; Wunderlich, Mark; Guzman, Monica L; Jegga, Anil G; Zeleznik-Le, Nancy J; Chen, Jianjun; Mulloy, James C; Cancelas, Jose A; Jordan, Craig T; Aronow, Bruce J; Marcucci, Guido; Bhat, Balkrishen; Gebelein, Brian; Grimes, H Leighton (2014. ) Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity.The Journal of clinical investigation, , 124 (1 ) ,222-36

Khandanpour, Cyrus; Phelan, James D; Vassen, Lothar; Schütte, Judith; Chen, Riyan; Horman, Shane R; Gaudreau, Marie-Claude; Krongold, Joseph; Zhu, Jinfang; Paul, William E; Dührsen, Ulrich; Göttgens, Bertie; Grimes, H Leighton; Möröy, Tarik (2013. ) Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia.Cancer cell, , 23 (2 ) ,200-14

Phelan, James D; Saba, Ingrid; Zeng, Hui; Kosan, Christian; Messer, Malynda S; Olsson, H Andre; Fraszczak, Jennifer; Hildeman, David A; Aronow, Bruce J; Möröy, Tarik; Grimes, H Leighton (2013. ) Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors.PLoS genetics, , 9 (9 ) ,e1003713

Meyer, Sara E; Hasenstein, Jason R; Baktula, Avinash; Velu, Chinavenmani S; Xu, Yan; Wan, Huajing; Whitsett, Jeffrey A; Gilks, C Blake; Grimes, H Leighton (2010. ) Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival.The American journal of pathology, , 177 (3 ) ,1503-13

Phelan, James D; Shroyer, Noah F; Cook, Tiffany; Gebelein, Brian; Grimes, H Leighton (2010. ) Gfi1-cells and circuits: unraveling transcriptional networks of development and disease.Current opinion in hematology, , 17 (4 ) ,300-7

Dwivedi, Pankaj; Chutipongtanate, Somchai; Muench, David E; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D (2020. ) SWATH-Proteomics of Ibrutinib's Action in Myeloid Leukemia Initiating Mutated G-CSFR Signaling.Proteomics. Clinical applications, , e1900144

Hinge, Ashwini; He, Jingyi; Bartram, James; Javier, Jose; Xu, Juying; Fjellman, Ellen; Sesaki, Hiromi; Li, Tingyu; Yu, Jie; Wunderlich, Mark; Mulloy, James; Kofron, Matthew; Salomonis, Nathan; Grimes, H Leighton; Filippi, Marie-Dominique (2020. ) Asymmetrically Segregated Mitochondria Provide Cellular Memory of Hematopoietic Stem Cell Replicative History and Drive HSC Attrition.Cell stem cell, , 26 (3 ) ,420-430.e6

Yue, Lanzhu; Sharma, Vasundhara; Horvat, Nathan P; Akuffo, Afua A; Beatty, Matthew S; Murdun, Cem; Colin, Christelle; Billington, Julia M R; Goodheart, William E; Sahakian, Eva; Zhang, Ling; Powers, John J; Amin, Narmin E; Lambert-Showers, Que T; Darville, Lancia N; Pinilla-Ibarz, Javier; Reuther, Gary W; Wright, Kenneth L; Conti, Chiara; Lee, Jennifer Y; Zheng, Xiaozhang; Ng, Pui Yee; Martin, Matthew W; Marshall, C Gary; Koomen, John M; Levine, Ross L; Verma, Amit; Grimes, H Leighton; Sotomayor, Eduardo M; Shao, Zonghong; Epling-Burnette, Pearlie K (2020. ) HDAC11 deficiency disrupts oncogene-induced hematopoiesis in myeloproliferative neoplasms.Blood, , 135 (3 ) ,191-207

Lucas, Daniel; Salomonis, Nathan; Grimes, H Leighton (2020. ) Unraveling bone marrow architecture.Nature cell biology, , 22 (1 ) ,5-6

Horman, Shane R; Velu, Chinavenmeni S; Chaubey, Aditya; Bourdeau, Tristan; Zhu, Jinfang; Paul, William E; Gebelein, Brian; Grimes, H Leighton (2009. ) Gfi1 integrates progenitor versus granulocytic transcriptional programming.Blood, , 113 (22 ) ,5466-75

DePasquale, Erica A K; Schnell, Daniel; Dexheimer, Phillip; Ferchen, Kyle; Hay, Stuart; Chetal, Kashish; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Salomonis, Nathan (2019. ) cellHarmony: cell-level matching and holistic comparison of single-cell transcriptomes.Nucleic acids research, , 47 (21 ) ,e138

Velu, Chinavenmeni S; Baktula, Avinash M; Grimes, H Leighton (2009. ) Gfi1 regulates miR-21 and miR-196b to control myelopoiesis.Blood, , 113 (19 ) ,4720-8

DePasquale, Erica A K; Schnell, Daniel J; Van Camp, Pieter-Jan; Valiente-Alandí, Íñigo; Blaxall, Burns C; Grimes, H Leighton; Singh, Harinder; Salomonis, Nathan (2019. ) DoubletDecon: Deconvoluting Doublets from Single-Cell RNA-Sequencing Data.Cell reports, , 29 (6 ) ,1718-1727.e8

Gu, YuanYuan; Harley, Isaac T W; Henderson, Lindsay B; Aronow, Bruce J; Vietor, Ilja; Huber, Lukas A; Harley, John B; Kilpatrick, Jeffrey R; Langefeld, Carl D; Williams, Adrienne H; Jegga, Anil G; Chen, Jing; Wills-Karp, Marsha; Arshad, S Hasan; Ewart, Susan L; Thio, Chloe L; Flick, Leah M; Filippi, Marie-Dominique; Grimes, H Leighton; Drumm, Mitchell L; Cutting, Garry R; Knowles, Michael R; Karp, Christopher L (2009. ) Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease.Nature, , 458 (7241 ) ,1039-42

Adelman, Emmalee R; Huang, Hsuan-Ting; Roisman, Alejandro; Olsson, André; Colaprico, Antonio; Qin, Tingting; Lindsley, R Coleman; Bejar, Rafael; Salomonis, Nathan; Grimes, H Leighton; Figueroa, Maria E (2019. ) Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.Cancer discovery, , 9 (8 ) ,1080-1101

Duy, Cihangir; Teater, Matt; Garrett-Bakelman, Francine E; Lee, Tak C; Meydan, Cem; Glass, Jacob L; Li, Meng; Hellmuth, Johannes C; Mohammad, Helai P; Smitheman, Kimberly N; Shih, Alan H; Abdel-Wahab, Omar; Tallman, Martin S; Guzman, Monica L; Muench, David; Grimes, H Leighton; Roboz, Gail J; Kruger, Ryan G; Creasy, Caretha L; Paietta, Elisabeth M; Levine, Ross L; Carroll, Martin; Melnick, Ari M (2019. ) Rational Targeting of Cooperating Layers of the Epigenome Yields Enhanced Therapeutic Efficacy against AML.Cancer discovery, , 9 (7 ) ,872-889

Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Virendra K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton (2019. ) Author Correction: Single-cell analysis of mixed-lineage states leading to a binary cell fate choice.Nature, , 569 (7755 ) ,E3

Li-Kroeger, David; Witt, Lorraine M; Grimes, H Leighton; Cook, Tiffany A; Gebelein, Brian (2008. ) Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS.Developmental cell, , 15 (2 ) ,298-308

Park, Derek S; Akuffo, Afua A; Muench, David E; Grimes, H Leighton; Epling-Burnette, Pearlie K; Maini, Philip K; Anderson, Alexander R A; Bonsall, Michael B (2019. ) Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation.PLoS computational biology, , 15 (4 ) ,e1006913

Zarebski, Adrian; Velu, Chinavenmeni S; Baktula, Avinash M; Bourdeau, Tristan; Horman, Shane R; Basu, Sudeep; Bertolone, Salvatore J; Horwitz, Marshal; Hildeman, David A; Trent, John O; Grimes, H Leighton (2008. ) Mutations in growth factor independent-1 associated with human neutropenia block murine granulopoiesis through colony stimulating factor-1.Immunity, , 28 (3 ) ,370-80

Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D (2019. ) Phospho serine and threonine analysis of normal and mutated granulocyte colony stimulating factor receptors.Scientific data, , 6 (1 ) ,21

Lee, Catherine; Rudneva, Vasilisa A; Erkek, Serap; Zapatka, Marc; Chau, Lianne Q; Tacheva-Grigorova, Silvia K; Garancher, Alexandra; Rusert, Jessica M; Aksoy, Ozlem; Lea, Robin; Mohammad, Helai P; Wang, Jianxun; Weiss, William A; Grimes, H Leighton; Pfister, Stefan M; Northcott, Paul A; Wechsler-Reya, Robert J (2019. ) Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma.Nature communications, , 10 (1 ) ,332

Dwivedi, Pankaj; Muench, David E; Wagner, Michael; Azam, Mohammad; Grimes, H Leighton; Greis, Kenneth D (2019. ) Time resolved quantitative phospho-tyrosine analysis reveals Bruton's Tyrosine kinase mediated signaling downstream of the mutated granulocyte-colony stimulating factor receptors.Leukemia, , 33 (1 ) ,75-87

Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S (2018. ) The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification.Cell reports, , 25 (11 ) ,3229

Kazanjian, Avedis; Gross, Eleanore A; Grimes, H Leighton (2006. ) The growth factor independence-1 transcription factor: new functions and new insights.Critical reviews in oncology/hematology, , 59 (2 ) ,85-97

Hay, Stuart B; Ferchen, Kyle; Chetal, Kashish; Grimes, H Leighton; Salomonis, Nathan (2018. ) The Human Cell Atlas bone marrow single-cell interactive web portal.Experimental hematology, , 68 ,51-61

Muench, David E; Ferchen, Kyle; Velu, Chinavenmeni S; Pradhan, Kith; Chetal, Kashish; Chen, Xiaoting; Weirauch, Matthew T; Colmenares, Clemencia; Verma, Amit; Salomonis, Nathan; Grimes, H Leighton (2018. ) SKI controls MDS-associated chronic TGF-? signaling, aberrant splicing, and stem cell fitness.Blood, , 132 (21 ) ,e24-e34

Lu, Yi-Chien; Sanada, Chad; Xavier-Ferrucio, Juliana; Wang, Lin; Zhang, Ping-Xia; Grimes, H Leighton; Venkatasubramanian, Meenakshi; Chetal, Kashish; Aronow, Bruce; Salomonis, Nathan; Krause, Diane S (2018. ) The Molecular Signature of Megakaryocyte-Erythroid Progenitors Reveals a Role for the Cell Cycle in Fate Specification.Cell reports, , 25 (8 ) ,2083-2093.e4

Kazanjian, Avedis; Wallis, Deeann; Au, Nicholas; Nigam, Rupesh; Venken, Koen J T; Cagle, Philip T; Dickey, Burton F; Bellen, Hugo J; Gilks, C Blake; Grimes, H Leighton (2004. ) Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells.Cancer research, , 64 (19 ) ,6874-82

Hayashi, Yoshihiro; Zhang, Yue; Yokota, Asumi; Yan, Xiaomei; Liu, Jinqin; Choi, Kwangmin; Li, Bing; Sashida, Goro; Peng, Yanyan; Xu, Zefeng; Huang, Rui; Zhang, Lulu; Freudiger, George M; Wang, Jingya; Dong, Yunzhu; Zhou, Yile; Wang, Jieyu; Wu, Lingyun; Bu, Jiachen; Chen, Aili; Zhao, Xinghui; Sun, Xiujuan; Chetal, Kashish; Olsson, Andre; Watanabe, Miki; Romick-Rosendale, Lindsey E; Harada, Hironori; Shih, Lee-Yung; Tse, William; Bridges, James P; Caligiuri, Michael A; Huang, Taosheng; Zheng, Yi; Witte, David P; Wang, Qian-Fei; Qu, Cheng-Kui; Salomonis, Nathan; Grimes, H Leighton; Nimer, Stephen D; Xiao, Zhijian; Huang, Gang (2018. ) Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes.Cancer discovery, , 8 (11 ) ,1438-1457

Meyer, Sara E; Muench, David E; Rogers, Andrew M; Newkold, Tess J; Orr, Emily; O'Brien, Eric; Perentesis, John P; Doench, John G; Lal, Ashish; Morris, Patrick J; Thomas, Craig J; Lieberman, Judy; McGlinn, Edwina; Aronow, Bruce J; Salomonis, Nathan; Grimes, H Leighton (2018. ) miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.The Journal of experimental medicine, , 215 (8 ) ,2115-2136

Zhang, Cuiping; D'Alessandro, Angelo; Wellendorf, Ashley M; Mohmoud, Fatima; Serrano-Lopez, Juana; Perentesis, John P; Komurov, Kakajan; Alexe, Gabriela; Stegmaier, Kimberly; Whitsett, Jeffrey A; Grimes, H Leighton; Cancelas, Jose A (2018. ) KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia.Oncotarget, , 9 (51 ) ,29665-29679

Park, Jung-Hyun; Yu, Qing; Erman, Batu; Appelbaum, Jacob S; Montoya-Durango, Diego; Grimes, H Leighton; Singer, Alfred (2004. ) Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival.Immunity, , 21 (2 ) ,289-302

Zhou, Yile; Yan, Xiaomei; Feng, Xiaomin; Bu, Jiachen; Dong, Yunzhu; Lin, Peipei; Hayashi, Yoshihiro; Huang, Rui; Olsson, Andre; Andreassen, Paul R; Grimes, H Leighton; Wang, Qian-Fei; Cheng, Tao; Xiao, Zhijian; Jin, Jie; Huang, Gang (2018. ) Setd2 regulates quiescence and differentiation of adult hematopoietic stem cells by restricting RNA polymerase II elongation.Haematologica, , 103 (7 ) ,1110-1123

Doan, Loretta L; Porter, Susan D; Duan, Zhijun; Flubacher, Marcella M; Montoya, Diego; Tsichlis, Philip N; Horwitz, Marshall; Gilks, C Blake; Grimes, H Leighton (2004. ) Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells.Nucleic acids research, , 32 (8 ) ,2508-19

Kleeman, Benjamin; Olsson, Andre; Newkold, Tess; Kofron, Matt; DeLay, Monica; Hildeman, David; Grimes, H Leighton (2018. ) A guide to choosing fluorescent protein combinations for flow cytometric analysis based on spectral overlap.Cytometry. Part A : the journal of the International Society for Analytical Cytology, , 93 (5 ) ,556-562

Lee, Jung-Mi; Govindarajah, Vinothini; Goddard, Bryan; Hinge, Ashwini; Muench, David E; Filippi, Marie-Dominique; Aronow, Bruce; Cancelas, Jose A; Salomonis, Nathan; Grimes, H Leighton; Reynaud, Damien (2018. ) Obesity alters the long-term fitness of the hematopoietic stem cell compartment through modulation of Gfi1 expression.The Journal of experimental medicine, , 215 (2 ) ,627-644

Yáñez, Alberto; Coetzee, Simon G; Olsson, Andre; Muench, David E; Berman, Benjamin P; Hazelett, Dennis J; Salomonis, Nathan; Grimes, H Leighton; Goodridge, Helen S (2017. ) Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.Immunity, , 47 (5 ) ,890-902.e4

Person, Richard E; Li, Feng-Qian; Duan, Zhijun; Benson, Kathleen F; Wechsler, Jeremy; Papadaki, Helen A; Eliopoulos, George; Kaufman, Christina; Bertolone, Salvatore J; Nakamoto, Betty; Papayannopoulou, Thalia; Grimes, H Leighton; Horwitz, Marshall (2003. ) Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2.Nature genetics, , 34 (3 ) ,308-12

Fang, Jing; Barker, Brenden; Bolanos, Lyndsey; Liu, Xiaona; Jerez, Andres; Makishima, Hideki; Christie, Susanne; Chen, Xiaoting; Rao, Dinesh S; Grimes, H Leighton; Komurov, Kakajan; Weirauch, Matthew T; Cancelas, Jose A; Maciejewski, Jaroslaw P; Starczynowski, Daniel T (2014. ) Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-?B gene network.Cell reports, , 8 (5 ) ,1328-38

Doan, Loretta L; Kitay, Mary Kate; Yu, Qing; Singer, Alfred; Herblot, Sabine; Hoang, Trang; Bear, Susan E; Morse, Herbert C; Tsichlis, Philip N; Grimes, H Leighton (2003. ) Growth factor independence-1B expression leads to defects in T cell activation, IL-7 receptor alpha expression, and T cell lineage commitment. Journal of immunology (Baltimore, Md. : 1950), , 170 (5 ) ,2356-66

Northcott, Paul A; Lee, Catherine; Zichner, Thomas; Stütz, Adrian M; Erkek, Serap; Kawauchi, Daisuke; Shih, David J H; Hovestadt, Volker; Zapatka, Marc; Sturm, Dominik; Jones, David T W; Kool, Marcel; Remke, Marc; Cavalli, Florence M G; Zuyderduyn, Scott; Bader, Gary D; VandenBerg, Scott; Esparza, Lourdes Adriana; Ryzhova, Marina; Wang, Wei; Wittmann, Andrea; Stark, Sebastian; Sieber, Laura; Seker-Cin, Huriye; Linke, Linda; Kratochwil, Fabian; Jäger, Natalie; Buchhalter, Ivo; Imbusch, Charles D; Zipprich, Gideon; Raeder, Benjamin; Schmidt, Sabine; Diessl, Nicolle; Wolf, Stephan; Wiemann, Stefan; Brors, Benedikt; Lawerenz, Chris; Eils, Jürgen; Warnatz, Hans-Jörg; Risch, Thomas; Yaspo, Marie-Laure; Weber, Ursula D; Bartholomae, Cynthia C; von Kalle, Christof; Turányi, Eszter; Hauser, Peter; Sanden, Emma; Darabi, Anna; Siesjö, Peter; Sterba, Jaroslav; Zitterbart, Karel; Sumerauer, David; van Sluis, Peter; Versteeg, Rogier; Volckmann, Richard; Koster, Jan; Schuhmann, Martin U; Ebinger, Martin; Grimes, H Leighton; Robinson, Giles W; Gajjar, Amar; Mynarek, Martin; von Hoff, Katja; Rutkowski, Stefan; Pietsch, Torsten; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Eils, Roland; Gilbertson, Richard J; Korshunov, Andrey; Taylor, Michael D; Lichter, Peter; Korbel, Jan O; Wechsler-Reya, Robert J; Pfister, Stefan M (2014. ) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.Nature, , 511 (7510 ) ,428-34

Boespflug, Nicholas D; Kumar, Sachin; McAlees, Jaclyn W; Phelan, James D; Grimes, H Leighton; Hoebe, Kasper; Hai, Tsonwin; Filippi, Marie-Dominique; Karp, Christopher L (2014. ) ATF3 is a novel regulator of mouse neutrophil migration.Blood, , 123 (13 ) ,2084-93

Yáñez, Alberto; Goodridge, Helen S; Grimes, H Leighton (2017. ) Counting the cost of lineage decisions.Nature immunology, , 18 (8 ) ,872-873

Tidwell, Timothy; Wechsler, Jeremy; Nayak, Ramesh C; Trump, Lisa; Salipante, Stephen J; Cheng, Jerry C; Donadieu, Jean; Glaubach, Taly; Corey, Seth J; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A; Horwitz, Marshall S (2014. ) Neutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms.Blood, , 123 (4 ) ,562-9

Kesarwani, Meenu; Kincaid, Zachary; Gomaa, Ahmed; Huber, Erika; Rohrabaugh, Sara; Siddiqui, Zain; Bouso, Muhammad F; Latif, Tahir; Xu, Ming; Komurov, Kakajan; Mulloy, James C; Cancelas, Jose A; Grimes, H Leighton; Azam, Mohammad (2017. ) Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia.Nature medicine, , 23 (4 ) ,472-482

Goyama, Susumu; Schibler, Janet; Cunningham, Lea; Zhang, Yue; Rao, Yalan; Nishimoto, Nahoko; Nakagawa, Masahiro; Olsson, Andre; Wunderlich, Mark; Link, Kevin A; Mizukawa, Benjamin; Grimes, H Leighton; Kurokawa, Mineo; Liu, P Paul; Huang, Gang; Mulloy, James C (2013. ) Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells.The Journal of clinical investigation, , 123 (9 ) ,3876-88

Olsson, Andre; Venkatasubramanian, Meenakshi; Chaudhri, Viren K; Aronow, Bruce J; Salomonis, Nathan; Singh, Harinder; Grimes, H Leighton (2016. ) Single-cell analysis of mixed-lineage states leading to a binary cell fate choice.Nature, , 537 (7622 ) ,698-702

Raines, Anna M; Adam, Mike; Magella, Bliss; Meyer, Sara E; Grimes, H Leighton; Dey, Sudhansu K; Potter, S Steven (2013. ) Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts.Development (Cambridge, England), , 140 (14 ) ,2942-52

Meyer, Sara E; Qin, Tingting; Muench, David E; Masuda, Kohei; Venkatasubramanian, Meenakshi; Orr, Emily; Suarez, Lauren; Gore, Steven D; Delwel, Ruud; Paietta, Elisabeth; Tallman, Martin S; Fernandez, Hugo; Melnick, Ari; Le Beau, Michelle M; Kogan, Scott; Salomonis, Nathan; Figueroa, Maria E; Grimes, H Leighton (2016. ) DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia.Cancer discovery, , 6 (5 ) ,501-15

Horwitz, Marshall S; Corey, Seth J; Grimes, H Leighton; Tidwell, Timothy (2013. ) ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology.Hematology/oncology clinics of North America, , 27 (1 ) ,19-41, vii

Muench, David E; Grimes, H Leighton (2015. ) Transcriptional Control of Stem and Progenitor Potential.Current stem cell reports, , 1 (3 ) ,139-150

Unnisa, Zeenath; Clark, Jason P; Roychoudhury, Jayeeta; Thomas, Elizabeth; Tessarollo, Lino; Copeland, Neal G; Jenkins, Nancy A; Grimes, H Leighton; Kumar, Ashish R (2012. ) Meis1 preserves hematopoietic stem cells in mice by limiting oxidative stress.Blood, , 120 (25 ) ,4973-81

Nayak, Ramesh C; Trump, Lisa R; Aronow, Bruce J; Myers, Kasiani; Mehta, Parinda; Kalfa, Theodosia; Wellendorf, Ashley M; Valencia, C Alexander; Paddison, Patrick J; Horwitz, Marshall S; Grimes, H Leighton; Lutzko, Carolyn; Cancelas, Jose A (2015. ) Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells.The Journal of clinical investigation, , 125 (8 ) ,3103-16

Khandanpour, Cyrus; Krongold, Joseph; Schütte, Judith; Bouwman, Frederique; Vassen, Lothar; Gaudreau, Marie-Claude; Chen, Riyan; Calero-Nieto, Fernando J; Diamanti, Evangelia; Hannah, Rebecca; Meyer, Sara E; Grimes, H Leighton; van der Reijden, Bert A; Jansen, Joop H; Patel, Chandrashekhar V; Peeters, Justine K; Löwenberg, Bob; Dührsen, Ulrich; Göttgens, Bertie; Möröy, Tarik (2012. ) The human GFI136N variant induces epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven myeloproliferative disorder in mice.Blood, , 120 (19 ) ,4006-17

Zhang, Yue; Yan, Xiaomei; Sashida, Goro; Zhao, Xinghui; Rao, Yalan; Goyama, Susumu; Whitman, Susan P; Zorko, Nicholas; Bernot, Kelsie; Conway, Rajeana M; Witte, David; Wang, Qian-Fei; Tenen, Daniel G; Xiao, Zhijian; Marcucci, Guido; Mulloy, James C; Grimes, H Leighton; Caligiuri, Michael A; Huang, Gang (2012. ) Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells.Blood, , 120 (5 ) ,1118-29

Stoffers, Sara L; Meyer, Sara E; Grimes, H Leighton (2012. ) MicroRNAs in the midst of myeloid signal transduction.Journal of cellular physiology, , 227 (2 ) ,525-33

Velu, Chinavenmeni S; Grimes, H Leighton (2012. ) Utilizing antagomiR (antisense microRNA) to knock down microRNA in murine bone marrow cells.Methods in molecular biology (Clifton, N.J.), , 928 ,185-95

D'Souza, Sonia; del Prete, Davide; Jin, Shunqian; Sun, Quanhong; Huston, Alissa J; Kostov, Flavia Esteve; Sammut, Benedicte; Hong, Chang-Sook; Anderson, Judith L; Patrene, Kenneth D; Yu, Shibing; Velu, Chinavenmeni S; Xiao, Guozhi; Grimes, H Leighton; Roodman, G David; Galson, Deborah L (2011. ) Gfi1 expressed in bone marrow stromal cells is a novel osteoblast suppressor in patients with multiple myeloma bone disease.Blood, , 118 (26 ) ,6871-80

McClendon, A Kathleen; Dean, Jeffry L; Ertel, Adam; Fu, Zhiyan; Rivadeneira, Dayana B; Reed, Christopher A; Bourgo, Ryan J; Witkiewicz, Agnieszka; Addya, Sankar; Mayhew, Christopher N; Grimes, H Leighton; Fortina, Paolo; Knudsen, Erik S (2011. ) RB and p53 cooperate to prevent liver tumorigenesis in response to tissue damage.Gastroenterology, , 141 (4 ) ,1439-50

Kurtulus, Sema; Tripathi, Pulak; Moreno-Fernandez, Maria E; Sholl, Allyson; Katz, Jonathan D; Grimes, H Leighton; Hildeman, David A (2011. ) Bcl-2 allows effector and memory CD8+ T cells to tolerate higher expression of Bim.Journal of immunology (Baltimore, Md. : 1950), , 186 (10 ) ,5729-37

Guo, Fukun; Zhang, Shuangmin; Tripathi, Pulak; Mattner, Jochen; Phelan, James; Sproles, Alyssa; Mo, Jun; Wills-Karp, Marsha; Grimes, H Leighton; Hildeman, David; Zheng, Yi (2011. ) Distinct roles of Cdc42 in thymopoiesis and effector and memory T cell differentiation.PloS one, , 6 (3 ) ,e18002

Guo, Fukun; Hildeman, David; Tripathi, Pulak; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi (2010. ) Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis.Proceedings of the National Academy of Sciences of the United States of America, , 107 (43 ) ,18505-10

Tripathi, Pulak; Kurtulus, Sema; Wojciechowski, Sara; Sholl, Allyson; Hoebe, Kasper; Morris, Suzanne C; Finkelman, Fred D; Grimes, H Leighton; Hildeman, David A (2010. ) STAT5 is critical to maintain effector CD8+ T cell responses.Journal of immunology (Baltimore, Md. : 1950), , 185 (4 ) ,2116-24

Kong, Kimi Y; Owens, Kristin S; Rogers, Jason H; Mullenix, Jason; Velu, Chinavenmeni S; Grimes, H Leighton; Dahl, Richard (2010. ) MIR-23A microRNA cluster inhibits B-cell development.Experimental hematology, , 38 (8 ) ,629-640.e1

Sharif-Askari, Ehssan; Vassen, Lothar; Kosan, Christian; Khandanpour, Cyrus; Gaudreau, Marie-Claude; Heyd, Florian; Okayama, Taro; Jin, Jianmin; Rojas, Meghan E B; Grimes, H Leighton; Zeng, Hui; Möröy, Tarik (2010. ) Zinc finger protein Gfi1 controls the endotoxin-mediated Toll-like receptor inflammatory response by antagonizing NF-kappaB p65.Molecular and cellular biology, , 30 (16 ) ,3929-42

Barnes, Michael J; Aksoylar, Halil; Krebs, Philippe; Bourdeau, Tristan; Arnold, Carrie N; Xia, Yu; Khovananth, Kevin; Engel, Isaac; Sovath, Sosathya; Lampe, Kristin; Laws, Eleana; Saunders, Amy; Butcher, Geoffrey W; Kronenberg, Mitchell; Steinbrecher, Kris; Hildeman, David; Grimes, H Leighton; Beutler, Bruce; Hoebe, Kasper (2010. ) Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice.Journal of immunology (Baltimore, Md. : 1950), , 184 (7 ) ,3743-54

Guo, Fukun; Velu, Chinavenmeni S; Grimes, H Leighton; Zheng, Yi (2009. ) Rho GTPase Cdc42 is essential for B-lymphocyte development and activation.Blood, , 114 (14 ) ,2909-16

Arumugam, Paritha I; Urbinati, Fabrizia; Velu, Chinavenmeni S; Higashimoto, Tomoyasu; Grimes, H Leighton; Malik, Punam (2009. ) The 3' region of the chicken hypersensitive site-4 insulator has properties similar to its core and is required for full insulator activity.PloS one, , 4 (9 ) ,e6995

Salipante, Stephen J; Rojas, Meghan E B; Korkmaz, Brice; Duan, Zhijun; Wechsler, Jeremy; Benson, Kathleen F; Person, Richard E; Grimes, H Leighton; Horwitz, Marshall S (2009. ) Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase.Molecular and cellular biology, , 29 (16 ) ,4394-405

Popovic, Relja; Riesbeck, Laurie E; Velu, Chinavenmeni S; Chaubey, Aditya; Zhang, Jiwang; Achille, Nicholas J; Erfurth, Frank E; Eaton, Katherine; Lu, Jun; Grimes, H Leighton; Chen, Jianjun; Rowley, Janet D; Zeleznik-Le, Nancy J (2009. ) Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization.Blood, , 113 (14 ) ,3314-22

Montoya-Durango, Diego E; Velu, Chinavenmeni S; Kazanjian, Avedis; Rojas, Meghan E B; Jay, Chris M; Longmore, Gregory D; Grimes, H Leighton (2008. ) Ajuba functions as a histone deacetylase-dependent co-repressor for autoregulation of the growth factor-independent-1 transcription factor.The Journal of biological chemistry, , 283 (46 ) ,32056-65

Duan, Zhijun; Person, Richard E; Lee, Hu-Hui; Huang, Shi; Donadieu, Jean; Badolato, Raffaele; Grimes, H Leighton; Papayannopoulou, Thalia; Horwitz, Marshall S (2007. ) Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5.Molecular and cellular biology, , 27 (19 ) ,6889-902

Wojciechowski, Sara; Tripathi, Pulak; Bourdeau, Tristan; Acero, Luis; Grimes, H Leighton; Katz, Jonathan D; Finkelman, Fred D; Hildeman, David A (2007. ) Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis.The Journal of experimental medicine, , 204 (7 ) ,1665-75

Linnoila, R Ilona; Jensen-Taubman, Sandra; Kazanjian, Avedis; Grimes, H Leighton (2007. ) Loss of GFI1 impairs pulmonary neuroendorine cell proliferation, but the neuroendocrine phenotype has limited impact on post-naphthalene airway repair.Laboratory investigation; a journal of technical methods and pathology, , 87 (4 ) ,336-44

Duan, Zhijun; Zarebski, Adrian; Montoya-Durango, Diego; Grimes, H Leighton; Horwitz, Marshall (2005. ) Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1.Molecular and cellular biology, , 25 (23 ) ,10338-51

Dwivedi, Prem P; Anderson, Paul H; Omdahl, John L; Grimes, H Leighton; Morris, Howard A; May, Brian K (2005. ) Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells.Endocrine-related cancer, , 12 (2 ) ,351-65

Grimes, H Leighton; Schanie, Carrie L; Huang, Yiming; Cramer, Daniel; Rezzoug, Francine; Fugier-Vivier, Isabelle; Ildstad, Suzanne T (2004. ) Graft facilitating cells are derived from hematopoietic stem cells and functionally require CD3, but are distinct from T lymphocytes.Experimental hematology, , 32 (10 ) ,946-54

Huang, Yiming; Rezzoug, Francine; Chilton, Paula M; Grimes, H Leighton; Cramer, Daniel E; Ildstad, Suzanne T (2004. ) Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment.Blood, , 104 (3 ) ,873-80

McGhee, Laura; Bryan, Josh; Elliott, Liza; Grimes, H Leighton; Kazanjian, Avedis; Davis, J Nathan; Meyers, Shari (2003. ) Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism.Journal of cellular biochemistry, , 89 (5 ) ,1005-18

Doan, Loretta L; Tanner, Michael K; Grimes, H Leighton (2003. ) Intranuclear staining of proteins in heterogeneous cell populations and verification of nuclear localization by flow cytometric analysis.Journal of immunological methods, , 279 (1-2 ) ,193-8

Wallis, Deeann; Hamblen, Melanie; Zhou, Yi; Venken, Koen J T; Schumacher, Armin; Grimes, H Leighton; Zoghbi, Huda Y; Orkin, Stuart H; Bellen, Hugo J (2003. ) The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival.Development (Cambridge, England), , 130 (1 ) ,221-32

Keywords

cancer, leukemia, hematopoiesis, blood, bone marrow failure, neutropenia, pediatric oncology, oncogene, models, therapy

Contact Information

Academic - Cincinnati Children's Hospital
Division of Immunobiology
Phone: 513-636-6089
Lee.Grimes@cchmc.org